Publication: Neuropeptide w alleviates hepatorenal oxidative damage in sepsis-induced rats
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Date
2020-05-01
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Abstract
Background: Despite modern surgical, medical and intensive care treatments, sepsis is still
one of the most frequent causes of morbidity and mortality due to multiple life-threatening
organ dysfunctions. We aimed to investigate the possible protective effect of neuropeptide
W (NPW), a novel peptide effective in regulating neuroendocrine functions, against sepsisinduced hepatorenal damage. Methods: In male Sprague-Dawley rats (200–250 g), sepsis
was induced by cecal ligation and puncture under ketamine anesthesia (n=48). Immediately
after surgery, saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) plus antibiotic (ceftriaxon;
100 mg/kg) (ET+C) or NPW (0.1, 0.3, 1 or 3 mg/kg) was given subcutaneously, and repeated
at 12th and 24th hours, while sham-operated control group (n=8) received three saline
injections within twenty-four hours. Rats were decapitated at the 25th hour of surgery and
C-reactive protein (CRP), corticosterone and IL-6 levels were measured in serum samples.
Kidney and liver samples were obtained for the measurement of myeloperoxidase activity
(MPO), malondialdehyde and glutathione levels and nuclear factor kappa-B (NF-kB) mRNA
expression levels. Histopathological evaluations were performed in hematoxylin-eosin-stained
samples. ANOVA and Student's t-tests were used for data analysis. Results: Elevated serum
levels of IL-6, corticosterone and CRP (p<0.05-0.01) in saline-treated sepsis group, as
compared to controls, were depressed in the ET+C- (p<0.05) or NPW- (p<0.05-0.001)
treated groups. Hepatic malondialdehyde and MPO levels, which were increased in salinetreated sepsis group (p<0.05 and p<0.001), were decreased by ET+C- (p<0.01) or NPW
(p<0.05-0.001) treatments. Similarly, increased renal malondialdehyde level was depressed
by NPW (p<0.05), but not by ET+C; while none of the treatments had an inhibitory effect
on renal MPO. In contrast to replenished renal glutathione levels by all treatments, hepatic
glutathione content was not changed by any of the treatments. Hepatic and renal NF-kB
mRNA expressions were similar in all groups. Severe hepatocyte degeneration, sinusoidal
congestion and inflammatory cell infiltration were observed in saline-treated sepsis group,
while parenchymal degeneration, congestion and Kupffer cell activation were mild in ET+Cand NPW-treated sepsis groups. Similarly, severe degeneration of renal corpuscles and
tubules with glomerular and interstitial congestion in the saline-treated sepsis group was
replaced by moderate glomerular and interstitial vascular congestion and mild tubular
congestion in both NPW- and ET+C-treated groups. Conclusion: NPW, applied during the
first 24 hours of sepsis, exerted a dose-dependent protective effect against hepatorenal
damage, which appears to involve an inhibitor
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ATICI A. E., ARABACI TAMER S., levent h. n., PEKER EYÜBOĞLU İ., ERCAN F., AKKİPRİK M., YEGEN B., \"NEUROPEPTIDE W ALLEVIATES HEPATORENAL OXIDATIVE DAMAGE IN SEPSIS-INDUCED RATS\", Gastroentrology, Amerika Birleşik Devletleri, 1 - 02 Mayıs 2020